Chronic kidney disease-mineral and bone disorder (CKD-MBD) significantly contributes to cardiovascular morbidity and mortality in CKD patients, raising questions about the molecular mechanisms linking cardiac and bone abnormalities. In this study, adult male spontaneously hypertensive rats (SHRs) underwent 3/4 nephrectomy (Nx) to induce mild CKD-MBD, with sham-operated SHRs (SO) serving as controls. All animals were fed a standard diet containing 0.6 % phosphorus. Exhibiting renal dysfunction comparable to human CKD stage 2, Nx rats had higher levels of serum inorganic phosphate (Pi), calciprotein particles (CPPs), and myocardial phosphorus (P) without differences in serum PTH, FGF23, kidney and bone P content. Compared to controls, the experimental group showed features of lower bone turnover with reduced osteoblast and osteocyte numbers and decreased eroded perimeter, alongside myocardial hypertrophy and fibrosis. In bone and myocardium, reciprocal alterations of a tissue expression of Pi-transporters and MAPK-signals were found. Reduced bone turnover associated with a lower tissue expression of Slc20a1 (PiT1) and osteogenic Mapk1 (ERK2). In myocardium, Slc20a2 (PiT2) and phospho-ERK1/2 expression were upregulated at gene and protein levels in Nx rats versus controls. These findings suggest that, in the setting of CKD-associated Pi retention, maladaptive bone and myocardial responses are mediated by the dysregulation of Pi transporters and down-stream ERK1/2 signals.

Podocyte injury is a central feature of proteinuric glomerular diseases, including primary focal segmental glomerulosclerosis (pFSGS), leading to podocyte loss and progressive kidney dysfunction. We previously demonstrated that podocytes in pFSGS undergo significant molecular changes, including reduced expression of Wilms' tumor suppressor protein (WT-1), a key transcription factor for podocyte integrity. This study explores the molecular phenotype of podocytes in immune glomerulopathies, with a focus on WT-1 and markers of epithelial (podocin) and mesenchymal (desmin, vimentin, nestin) phenotypes in pFSGS. We conducted a quantitative immunomorphological analysis and confocal microscopy to assess glomerular expression of WT-1, podocin, desmin, vimentin, and nestin in kidney samples from patients with morphologically confirmed pFSGS (n = 14), IgA nephropathy (IgAN, n = 14) with CKD G1-3, and negative controls (NC, n = 12). NC samples were obtained from unaffected renal cortex during nephrectomy for malignant neoplasms (Fig. 1a). Patients with pFSGS exhibited nephrotic syndrome and typical glomerular alterations on light and electron microscopy (Fig. 1b, c), while IgAN showed milder proteinuria (Fig. 1d). Compared to controls, pFSGS demonstrated significantly lower glomerular expression of WT-1 and podocin, alongside elevated desmin and nestin levels (Fig. 2a). In the combined pFSGS and IgAN group, WT-1 and podocin expression correlated positively (r = 0.51, P < 0.013) and both markers inversely associated with proteinuria (WT-1: r = −0.49, P < 0.05; podocin: r = −0.52, P < 0.05). Notably, in pFSGS, WT-1 expression negatively correlated with desmin (r = −0.74, P < 0.05), and desmin localized predominantly in WT-1-negative podocytes (Fig. 2b). Our findings reveal significant downregulation of WT-1 and podocin, alongside upregulation of desmin and nestin, in the early stages of primary FSGS. These findings are suggestive for the genomic reprogramming of podocytes as part of the epithelial-mesenchymal transition, determining the structural and functional disorders of these cells, more prominent in pFSGS.

Considering a paucity of relevant data, the study aimed to evaluate an efficacy of treatment with immunosuppression (IST) combined with tonsillectomy (TE) in Caucasian patients with high-risk primary IgA-nephropathy (IgAN). The study enrolled cases of primary IgAN (n = 221, age 34 ± 11 years, 52% male) with eGFR >20 ml/min/1.73 m2 and at high risk of progression. The latter defined as (i) proteinuria >1 g/day or (ii) the probability of starting dialysis within 5 years >11% with at least one of the following morphological lesions: mesangial proliferation, endocapillary hypercellularity, and cellular crescents. All patients received immunosuppressive therapy (steroid monotherapy −73%, steroids with cyclophosphamide, mycophenolic acid, cyclosporine, or azathioprine −27%). The prospectively followed experimental group received IST combined with TE (IST + TE, n = 85), no earlier than 12 months before and no later than 12 months after the start of IST. In most patients, TE was performed before the start of IST (n = 52; 61.1%), and the median time between the IST start and TE was −0.9 (−3.7; 1.5) months. The historic control group comprised subjects undergone only immunosuppressive therapy without TE (IST, n = 136). The follow-up period was 32 (14; 67) months. Outcomes were overall (complete or partial) remission (OR), and progression as a composite of ESKD or eGFR decrease of >40% from baseline. Kaplan–Meyer curves and Cox regression models combined with pseudo-randomisation methods (1:1 propensity score matching (PSM) of comparison groups and inverse probability of treatment weighting) were applied to compare the efficacy of IST + TE with only IST. In 1:1 PSM groups, the cumulative proportions of cases with OR and composite outcome and times to event had significant differences in favour of the IST+TE group (Fig. 1A and B). In Cox regression models, the combination therapy was associated with a significantly increased probability of remissions and the decrease in the probability of composite end-point of the IgA-nephropathy progression by 80–87% (Fig. 2). Caucasian patients with high-risk IgAN can benefit from the immunosuppression combined with tonsillectomy to induce disease remission and delay progression.

Anti-CD38 monoclonal antibody Daratumumab is known to be more effective in achievement of hematologic response (HR) in relapsed/refractory plasma cell clonal disease e.g. multiple myeloma and AL-amyloidosis comparing with conventional clone-directed treatment (CDT). Moreover, Daratumumab-based regimens demonstrated some benefits in relapsed/refractory renal AL-amyloidosis with higher rate of renal response (RR) reaching 50%–80%. However, the data on the Daratumumab effects in relapsed/refractory non-amyloid monoclonal immunoglobulin related kidney disease (mIgKD) are limited. The aim of the study was to check the hypothesis that Daratumumab-based regimens are more effective in relapsed/refractory non-amyloid mIgKD than traditional CDT including proteasome inhibitors, immunomodulatory drugs, cyclophosphamide, and dexamethasone. We included 37 patients with morphologically proven non-amyloid mIgKD with available follow-up (FUP) of at least 12 months. According to disease course and treatment modalities patients were divided on three groups including those who received: (i) only bortezomib-based regimens as frontline conventional CDT (group 1 “one line only,” n = 22) or due to relapsed/refractory disease were treated with (ii) more than one line of conventional CDT (group 2 “next lines,” n = 7) or (iii) Daratumumab-based regimens (group 3 “Dara group,” n = 8). Daratumumab was given in standard doses i.e. 16 mg/kg weekly 8 doses and then every other weeks 8 doses. Baseline clinical parameters of the groups and morphological spectrum of renal disease are presented in the Figs 1 and 2, respectively. HR was estimated according to currently accepted criteria. Decrease in 24 h proteinuria <3.5 g/by 50% from the baseline and <0.5 g at the FUP was determined as partial and complete RR, respectively. RR was considered to be achieved in the absence of eGFR decline >25%. RR was assessed at 12 months from treatment initiation and at FUP. Differences were considered significant at p-values <0.05. Patients of group 1 were treated with bortezomib/cyclophosphamide/dexamethasone regimen with median number of cycles 4 (4; 6) and with autologous stem cell transplant as consolidation option in 7 cases. In the group 2 relapsed (n = 1) and refractory (n = 6) non-amyloid mIgKD cases were cured with other standard regimens including immunomodulatory drugs (lenalidomide, pomalidomide), melphalane, cyclophosphamide, ixazomib, elotuzumab with the median number of lines 3 (2; 3). In the Dara group only 1 patient received Daratumumab in monoregimen due to hematologic and renal relapse of non-malignant mIgKD. Other 7 refractory cases were managed with Daratumumab in combination with lenalidomide/dexamethasone (n = 2), bortezomib/cyclophosphamide/dexamethasone (n = 3) and as mono-agent (n = 2). Median FUPs were 56 (23; 85), 43 (14; 72) and 22 (20; 54) months in group 1, 2 and 3, respectively. At least partial HR was achieved in 95%, 57% and 75% in group 1, 2 and 3, respectively, and was more common in group 1 than in the group 2 (P = 0.01) (Fig. 3A). In the group 1 RR were registered in 64% and 73% at 12 months and FUP, respectively. RR achievement rate at 12 months and at FUP in the group 2 was the same (71%) as well as in the Dara group (25%) (Fig. 3B). In the Dara group RR rate at FUP was lower than in the group 1 (P = 0.018). Daratumumab treatment in relapse/refractory non-amyloid mIgKD does not seem to have good effects regarding HR and RR. However, further studies of larger cohorts are needed to investigate Daratumumab efficacy in severe refractory clonal disease with kidney involvement.

Preeclampsia is a disorder that can occur during pregnancy and is one of the leading causes of death among pregnant women. This disorder occurs after the 20th week of pregnancy and is characterized by arterial hypertension, proteinuria, fetoplacental, and multiple organ dysfunctions. Despite the long history of studying preeclampsia, its etiology and pathogenesis remain poorly understood, and therapy is symptomatic. One of the factors of the disorder is believed to be misfolded proteins that are prone to form amyloid aggregates. The CRD tests, utilizing the binding of the amyloid-specific dye Congo red to urine components, demonstrate high efficiency in diagnosing preeclampsia. However, these tests have also been found to be positive in other disorders with proteinuria, presumably associated with concomitant amyloidosis. To assess the limitations of the CRD tests, we examined urine congophilia and protein components mediating Congo red positivity in patients with proteinuria, including preeclampsia, amyloid and non-amyloid nephropathies. We stained the urine samples and calculated congophilia levels. We also assessed the contribution of large protein aggregates to congophilia values using ultracentrifugation and determined the molecular weights of congophilic urinary proteins using centrifugal concentrators. All proteinuric groups demonstrate positive results in the CRD tests and congophilia levels were more than two times higher compared with the control non-proteinuric groups (p <0.01). There was a strong correlation between urine protein excretion and congophilia in amyloid nephropathy (rs = 0.76), non-amyloid nephropathies (rs = 0.90), and preeclampsia (rs = 0.90). Removal of large aggregates from urine did not affect the congophilia levels. Separation of urine protein fractions revealed congophilic components in the range of 30-100 kDa, including monomeric serum albumin. Our results indicate limitations of CRD tests in preeclampsia diagnostics in women with renal disorders and underscore the need for further research on the mechanisms of Congo red binding with urine components.

ABSTRACT Background This prospective single-arm trial with historic controls evaluated the efficacy and safety of treatment based on a combination of rituximab, intravenous cyclophosphamide and corticosteroids (RCP) administered at lower cumulative doses for the induction of early remission in primary membranous nephropathy (PMN). Methods We prospectively enrolled 30 high-risk PMN patients with persistent nephrotic syndrome (NS) and elevated antibodies to the phospholipase A2 receptor who underwent RCP therapy. We compared the effectiveness of RCP with that of historic controls who received rituximab-based therapy (RTX, n = 15) or cyclosporine + corticosteroids (CSA, n = 42). The primary outcomes were complete remission (CR) and overall remission (OR) by Month 12 and the time to remission. Results In the RCP group, the OR and CR rates by 12 months (97% and 60%) were higher than those in the RTX group (60% and 7%, P ≤ .009) and the CSA group (50% and 24%, P ≤ .003). The median time to OR [2.8 (1.6–3.9) months] was shorter compared with RTX [7.1 (3.4–17.5) months, P = .008] and CSA [7.3 (6.0–13.6) months, P < .001]. In adjusted Cox regression, hazard ratios for OR and CR attainment for RCP versus other treatments were 5.2 (95% CI 2.8–9.6) and 4.8 (95% CI 2.2–10.3), respectively. Propensity score–matched group analyses confirmed these results. One serious adverse event occurred in the RCP group in the follow-up of 56 patient-years. Conclusions RCP therapy is considered effective and safe for inducing early remission in high-risk PMN patients.

Abstract Background and Aims AL-amyloidosis (AL) and monoclonal immunoglobulin (MIg) deposition disease are common types of MIg-related glomerulopathies (MIgG) and are well-studied including approaches to treatment and hematological and renal responses (RR) assessment. Other rare MIgG comprise very diverse patterns of glomerular injury e.g. proliferative glomerulonephritis with MIg deposition (PGNMID), C3-glomerulopathy, fibrillary glomerulonephritis etc. Although RR defined as decrease in 24 h proteinuria by 30% without kidney function decline was validated only for renal AL it is widely used for MIg deposition disease and rare MIgG without validation. Nevertheless, the best approach to RR assessment in rare MIgG is still unclear. To shed some light on this problem we performed this study. Method We retrospectively analyzed 31 patients with rare MIgG who were treated with clone-specific treatment and had available follow-up (FUP) ≥6 months (mo). The following morphological patterns were diagnosed: PGNMID (n = 9), C3-glomerulopathy (n = 9), thrombotic microangiopathy (n = 5), cryoglobulinemic glomerulonephritis (n = 3), fibrillary glomerulonephritis (n = 3), immunotactoid glomerulonephritis (n = 1) and membranous nephropathy (n = 1). Patients’ baseline parameters are shown on Fig. 1 as well as treatment modalities. Hematological response defined according to currently accepted criteria is demonstrated on Fig. 1. We evaluated two approaches to the RR assessment: 1) at least partial renal response (PR) defined as 24 h proteinuria decreased by 50% from the baseline and <3.5 g, and 2) according to Palladini's criteria for AL (AL-RR) i.e. 24 h proteinuria decreased by 30% from the baseline or <0.5 g. Both RR were considered as achieved only in the absence of estimated glomerular filtration rate (eGFR) decline >25%. Time points for RR assessment were 6, 12 and 24 mo from the clone-specific treatment initiation. Renal outcome was estimated as initiation of renal replacement therapy or eGFR <15 ml/min/1.73 m2 at the end of follow-up. Death-censored renal survival was analyzed by the Kaplan-Meier method. Cox regression analysis was applied to determine which RR was independently associated with long-term kidney outcome. P-value was assumed at <0.05. Median FUP was 19 (7; 50) mo. FUP ≥12 and ≥24 mo were available in 26 and 17 patients, respectively. Results Total number of patients who achieved AL-RR at any RR assessment time point was 22 (71%). At 6, 12 and 24 mo the achievement of AL-RR was registered in 17, 16 and 10 patients, respectively. PR cumulatively was achieved in 19 (61%) patients: at time points of 6, 12, and 24 mo it was registered in 14, 14 and 9 cases, respectively. The 5-year cumulative renal survival in those who had AL-RR was better than in not responders (Fig. 2A). Patients who ever achieved PR had better cumulative renal survival compared with patients with no renal remission (Fig. 2B). In univariate Cox regression analysis the achievement of AL-RR (Exp(β) 0.158 (95% CI 0.03; 0.819)) was associated with renal outcome as well as the achievement of PR (Exp(β) 0.074 (95% CI 0.09; 0.626)). In multivariate Cox regression model adjusted for eGFR at the time of kidney biopsy AL-RR vs no response was estimated as an independent predictor of renal long-term prognosis (Exp(β) 0.082 (95% CI 0.009; 0.725)) as well as eGFR (Exp(β) 0.89 (95% CI 0.821; 0.985)). The only independent predictor of renal outcome in the model including eGFR at the time of kidney biopsy (Exp(β) 0.85 (95% CI 0.72; 0.99), p = 0.05) was PR (Exp(β) 0.011 (95% CI 0; 0.547), p = 0.021). Conclusion The classical concept of complete and partial renal remission seems to be more appropriate for rare MIgG and requires further validation studies.

Abstract Background and Aims Vascular calcification associated with a maladaptive bone response is common in CKD and is a major cause of mortality (up to 60% depending on CKD stage). Alterations in several intracellular signaling pathways have been reported during the cellular phenotype transition and vascular calcification, however the initial phases of vascular remodeling in early CKD-MBD remain poorly understood. The aim of this study was to investigate the early molecular and cellular features of aortic remodeling prior to calcification in a model of mild CKD-MBD with low bone turnover. Method We induced CKD-MBD by 3/4 nephrectomy (Nx, n = 8) in adult male spontaneously hypertensive rats (SHR) with normal phosphate (Pi) intake (0.6%). Controls were sham-operated Wistar rats (n = 8) and SHR (n = 8). Chronic kidney injury and Pi exchange parameters, serum levels of calciprotein particles (CPPs), intact PTH, intact FGF23, dickkopf-1 and sclerostin, static bone histomorphometry, aortic morphology (H&E, Masson's trichrome, calcein, von Kossa stain), CD31, aSMA, nestin, Col1a1, PDGFR-beta, PiT1, LGR4 and intracellular signaling molecules—phospho-ERK1/2, active (non-phospho) beta-catenin, Hes1, Gli1 were analyzed by IHC with quantitative morphometry and IF after 4 months. Confocal microscopy was performed at the Centre for Collective Use of the Pavlov Institute of Physiology, Russian Academy of Sciences (Zeiss LSM 710). Results The study found that Nx rats with chronic kidney injury comparable to human CKD S2 exhibited lower bone turnover (Fig. 1). The Nx group had higher serum levels of Pi and CPPs vs. control group, but there were no differences in Pi-regulatory factors (Figs 1, 2b). Additionally, the Nx group showed aorta remodeling, which was characterized by an increase in intima thickness, cellularity, and collagen accumulation in the medial layer (Figs 1, 2a). The histological parameters of intimal remodeling and perivascular fibrosis were found to be directly correlated with serum levels of Pi and CPPs. In Nx, there was a decrease in medial αSMA expression accompanied by an increase in phospho-ERK1/2, PiT1, nestin, Gli1, beta-catenin, dickkopf-1, and an decrease in Hes1 immunomorphological staining (Figs 1, 2a, c). αSMA-negative cells demonstrated the expression of osteogenesis-related molecules, such as phospho-ERK1/2 (Fig. 2a, c), and occasionally, RunX2 (Fig. 2a). Phospho-ERK1/2 and PiT1 were found to co-localize in Nx (Fig. 2c). Intimal remodeling was observed, characterized by increased beta-catenin and nestin expression (Fig. 2c). Conclusion In mild CKD-MBD with low bone turnover, early intimal and medial aortic remodeling was associated with higher serum Pi and CPPs levels, and upregulation of PiT1, ERK1/2. In addition, other signals likely related to osteogenesis (RunX2, LGR4) and regulation of vascular progenitor cells (Nestin, Wnt, Notch, Hedgehog) may be implicated.

OBJECTIVE:An evaluation of podocyte's molecular phenotype alterations in primary focal segmental glomerulosclerosis (pFSGS) and IgA nephropathy (IgAN). MATERIAL AND METHODS:The exploratory study included 14 cases of morphologically confirmed pFSGS, 14 cases of IgAN, and 12 negative controls. The negative controls comprised samples of the unaltered renal cortex obtained during laparoscopic nephrectomy in patients with malignant neoplasms of the kidney and bladder and without proteinuria. A quantitative immunomorphological study of Wilms tumour protein (WT1) expression and mesenchymal markers of podocytes (desmin and vimentin) was conducted on all kidney samples. The co-expression of the aforementioned molecules was analysed using confocal microscopy. RESULTS:Cases of pFSGS exhibited nephrotic syndrome with proteinuria of 9.3 (3.1-14) g/24 and typical glomerular alterations in light microscopy and ultrastructural analysis. In the IgAN group, proteinuria was less severe (1.2 (0.7-1.6) g/24). The estimated glomerular filtration rate in pFSGS and IgAN was similar (pFSGS: 85 (53-103) ml/min/1.72 m², IgAN: 76 (52-87) ml/min/1.72 m²; p=0.40). In both pFSGS and IgAN, there was a reduction in WT1 expression in podocytes and an increase in vimentin expression when compared to negative controls. Compared to IgAN and controls, pFSGS exhibited a lower prevalence of glomerular WT1 expression and higher expression of desmin, which was predominantly localised in WT1-negative glomerular areas in confocal microscopy. In pFSGS, decreased nuclear expression of WT1 and increased expression of desmin were observed in the parietal epithelium of the glomerular capsule. CONCLUSION:Bidirectional alterations in the glomerular expression of WT1 and intermediate filament proteins are apparent in pFSGS and IgAN. These findings are suggestive for the genomic reprogramming of podocytes and the parietal epithelium of the glomerulus as part of the epithelial-mesenchymal transition, determining the structural and functional disorders of these cells, more prominent in pFSGS.

Abstract Background and Aims Patients with CKD have significantly increased cardiovascular risk, and heart failure is a leading cause of morbidity and mortality in these patients. Myocardial hypertrophy is a hallmark of cardiac remodeling and dysfunction in CKD and is known to be mediated by angiotensin II, catecholamines, hyperphosphatemia, hyperparathyroidism, increase in FGF23, decrease in Klotho and alterations in various signaling pathways including calcineurin, mitogen-activated protein kinase ERK1/2, calmodulin-dependent protein kinase II etc. Less well understood are the mechanisms of fibrosis and intramyocardial arterial remodeling in CKD, which may be related to hyperphosphatemia and decreased renal and systemic Klotho. The aim of this study was to evaluate the molecular and cellular features of myocardial remodeling in experimental mild CKD. Method We induced CKD by 3/4 nephrectomy (Nx) in adult male spontaneously hypertensive rats (SHR) with a follow-up period of 4 months. Animals were fed standard chow containing 0.6% phosphate. Sham-operated Wistar rats and SHR served as controls. We measured serum creatinine, renal interstitial fibrosis area, systolic blood pressure (BP), myocardial mass index (MMI), histological indices of myocardial hypertrophy, interstitial fibrosis and intramyocardial artery (IA) remodeling (H&E, Masson's trichrome, von Kossa stain), myocardial phosphorus content, serum levels of inorganic phosphate (Pi), PTH and FGF23. Myocardial expression of phosphate transporters PiT1, ERK1/2, WNT, BMP, Notch, Hedgehog signaling pathways and LRG4 molecules was evaluated by PCR-RT, IHC and IF (Zeiss LSM 710; study performed at the Centre for Collective Use “Confocal Microscopy” of the Pavlov Institute of Physiology, Russian Academy of Sciences). Results Chronic kidney injury and phosphate regulatory factors did not differ, whereas BP and MMI were higher in sham SHR vs. Wistar rats (Fig. 1). Nx rats showed features of mild chronic kidney injury before the elevation of serum PTH, FGF23 levels (Fig. 1). Myocardial P content and serum Pi were higher in Nx and in the combined SHR group and directly correlated with indices of IA remodeling. Cardiomyocyte diameter, myocardial interstitial and perivascular fibrosis were higher in Nx (Figs 1, 2a) and accompanied with upregulation in Ppp3ca mRNA (calcineurin A, Fig. 2b), Mapk1 mRNA (ERK2, Fig. 2b), phospho-ERK1/2 (Figs 1, 3), PiT1 (Figs 1, 2c), Lgr4 (Fig. 2c) and downregulation of Hes1 mRNA (Fig. 2b). PiT1 and pospho-ERK1/2 were co-expressed in IA media from SHR (Fig. 2c). In Nx, nestin and LGR4 were expressed by IA adventitia and media cells, myocardial interstitial cells, and occasionally co-localized (Fig. 2c). Hes1 expression was detected in IA and capillary endothelial cells and co-localised with Gli1 in IA media; Gli1 was also detected in cardiomyocyte nuclei (Fig. 2c). In SHR, beta-catenin expression in cardiomyocytes was more pronounced in Nx (Fig. 2c). Conclusion Mild CKD is associated with histological and molecular features of cardiomyocyte hypertrophy, myocardial fibrosis and intramyocardial arterial remodeling, which are probably modulated by phosphate redistribution and its tissue retention involving upregulation of PiT1 and ERK1/2, as well as alterations in signals related to progenitor regulation and myocyte hypertrophy.

Background: The quality of life (QoL) and the psychological burden of immunoglobulin A nephropathy (IgAN) have not been thoroughly studied.Aim: To analyze QoL and complaints of patients with IgAN and to test the hypothesis that QoL scores are associated with clinical and demographic variables.Patients and methods: The study included 221 patients with primary IgAN, confirmed by biopsy. None of patients had received immunosuppressive treatment. QOL was assessed using the Russian version of the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire, which includes general scales for measuring QoL independent of disease and kidney-specific scales. In additions to QoL parameters, the prevalence of patient complaints was examined. Routine clinical and demographic data were used as independent variables in multiple regression models.Results: General QoL scores in patients with IgAN were comparable to those of conditionally healthy individuals. On CKD-specific scales, the highest scores were reported for "work status" and "symptoms/problems", while the lowest were for "burden of kidney disease". Key stressors included the disease itself, dietary restrictions, fatigue and impact of the disease on appearance. Female sex, older age, lower albumin level, and higher average blood pressure were independently associated with reduced QoL.Conclusion: Although IgAN patients scored relatively high on most QoL scales, they endure a a significant psychological and social burden. Identifying and addressing the psychological and social factors influencing life under the strain of the disease can be crucial for for improving patient-centered outcomes in IgAN management.

Aim.To evaluate the efficacy of immunosuppressive therapy (IST) and tonsillectomy (TE) in patients with high-risk IgA nephropathy (IgAN). Materials and мethods. The retrospective study cohort included cases with primary IgAN (n=213, age 34±11 years, male 52%) at high risk of progression with clinical and morphological data collected. The follow-up was 26 (10; 61) months. The association of IST without TE (IST; n=141) or with TE (IST+TE; n=72) with the development of complete (PR), partial (PR) and overall (PR or PR, OR) remissions was investigated. Results. The incidence of achieving early PR or OR in the IST and IST+TE groups was 65.2% and 86.1%, respectively (p=0.002). The probability of early PR or OR was significantly increased in the IST+TE group compared to IST [HR 1.714 (1.214–2.420) and HR 3.410 (1.309–8.880), respectively]. IST+TE was associated with a 3- to 4-fold increase in the likelihood of PR or OR at the end of follow-up [HR 2.575 (1.679–3.950) and HR 4.768 (2.434–9.337), respectively]. Analyses using pseudorandomisation methods yielded similar results. Conclusion. TE may be effective for remission induction in high-risk IgAN.